11-72019260-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006185.4(NUMA1):​c.584+234G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 152,240 control chromosomes in the GnomAD database, including 64,144 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.92 ( 64144 hom., cov: 31)

Consequence

NUMA1
NM_006185.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.941

Publications

5 publications found
Variant links:
Genes affected
NUMA1 (HGNC:8059): (nuclear mitotic apparatus protein 1) This gene encodes a large protein that forms a structural component of the nuclear matrix. The encoded protein interacts with microtubules and plays a role in the formation and organization of the mitotic spindle during cell division. Chromosomal translocation of this gene with the RARA (retinoic acid receptor, alpha) gene on chromosome 17 have been detected in patients with acute promyelocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NUMA1NM_006185.4 linkc.584+234G>A intron_variant Intron 9 of 26 ENST00000393695.8 NP_006176.2 Q14980-1Q3SYK8Q4LE64

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NUMA1ENST00000393695.8 linkc.584+234G>A intron_variant Intron 9 of 26 1 NM_006185.4 ENSP00000377298.4 Q14980-1

Frequencies

GnomAD3 genomes
AF:
0.916
AC:
139317
AN:
152122
Hom.:
64111
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.837
Gnomad AMI
AF:
1.00
Gnomad AMR
AF:
0.854
Gnomad ASJ
AF:
0.955
Gnomad EAS
AF:
0.841
Gnomad SAS
AF:
0.882
Gnomad FIN
AF:
0.957
Gnomad MID
AF:
0.965
Gnomad NFE
AF:
0.976
Gnomad OTH
AF:
0.939
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.916
AC:
139407
AN:
152240
Hom.:
64144
Cov.:
31
AF XY:
0.912
AC XY:
67879
AN XY:
74448
show subpopulations
African (AFR)
AF:
0.836
AC:
34728
AN:
41520
American (AMR)
AF:
0.853
AC:
13053
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.955
AC:
3316
AN:
3472
East Asian (EAS)
AF:
0.841
AC:
4349
AN:
5172
South Asian (SAS)
AF:
0.882
AC:
4253
AN:
4824
European-Finnish (FIN)
AF:
0.957
AC:
10159
AN:
10620
Middle Eastern (MID)
AF:
0.963
AC:
283
AN:
294
European-Non Finnish (NFE)
AF:
0.976
AC:
66366
AN:
68018
Other (OTH)
AF:
0.940
AC:
1988
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
582
1164
1746
2328
2910
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
906
1812
2718
3624
4530
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.950
Hom.:
44863
Bravo
AF:
0.908
Asia WGS
AF:
0.870
AC:
3024
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.92
DANN
Benign
0.39
PhyloP100
-0.94
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs949326; hg19: chr11-71730306; API